Session Information

Autoimmunity and more broadly non-communicable diseases develop with the imbalance between anti- and pro-inflammatory immune cell subsets, leading to an uncontrolled and damaging inflammation. Evidences have shown that short chain fatty acids promote anti-inflammatory regulatory T cell protecting from type 1 diabetes, colitis and allergies in mice. In the present study, we investigated the benefits of short chain fatty acid acetate extend to other immune cells involved in tolerance, the regulatory B cells (Breg).

Methods:

For this purpose, we assessed the effect of acetate on Breg in vitro and in vivo through oral supplementation or intraperitoneal injections. The functions of acetate-induced Bregs were assessed i) in vitro using co-culture with naïve T cells to assess Th17 differenciation ii) in vivo with adoptive transfer of acetate-stimulated B cells in a model of collagen antibody-induced arthritis (CAIA). In addition, the effect of acetate was also evaluated on B cells from human samples.

Results:

We showed that both in vivo and in vitro acetate promoted Breg differentiation from B1a cells but not from B2 cells in mice. Acetate-induced Breg cells could protect from collagen antibody-induced arthritis development when adoptively transferred. These effects were neither through specific G-protein receptor activation nor HDAC inhibition but by inducing metabolic changes particularly in B1a cells by fueling TCA cycle. Similarly, we found that acetate also promotes human Breg cells through metabolic changes.

Conclusion:

This work suggest that acetate might be a promising therapeutic approach to restore Breg population in autoimmune diseases such as Rheumatoid Arthritis in which they are defective.